Direct involvement of community pharmacists in the sale of OTC medicines is expected to help prevent adverse drug reactions (ADRs) and enhance treatment efficacy. However, the extent of their actual involvement in OTC medicine sales remains insufficiently investigated. To address this, we retrospectively analyzed OTC medicine sales survey forms to assess the involvement of community pharmacists in OTC medicine sales, and identify drug-related problems (DRPs) requiring pharmaceutical decisions. All customers who visited the Yokohama Nishiguchi branch of WinPharma Co., Ltd. to purchase OTC medicines were included in the study. Community pharmacists were involved in all OTC medicine sales. Among the 821 customers who sought specific OTC medicines, product choice was changed based on pharmacist recommendation in 124 cases (15.1%), including cases recommended to visit a doctor. Frequency of product change was highest for second-class OTC medicine sales. In addition, contraindications (21.0%) were the most common DRPs, with second-class OTC medicines accounting for 80.8% of all these cases. Furthermore, when including the 666 cases in which community pharmacists were consulted directly about purchasing OTC medicines, 790 of the 1487 cases (53.1%) required pharmacist involvement. These findings highlight the crucial role of community pharmacists preventing ADRs and enhancing treatment efficacy based on OTC medicines characteristics and conditions and lifestyles of users regardless of the risk classification of OTC medicines. Proactive involvement by community pharmacists can improve self-medication safety and efficacy by ensuring the proper use of OTC medicines.